PDK1 and Alzheimer disease: The explored mechanisms behind defective insulin signaling in the AD brain have included each of the following ordered steps leading to Akt (protein kinase B, PKB) activation [14,15]: decline in insulin receptor (IR) number, decline in ligand affinity, tyrosine kinase deactivation, inhibitory phosphorylation of insulin receptor substrate (IRS-1, via p70S6K), reduced PI3K (p85) activation, and impairment of the coordinated PDK-1- and mTORC2-dependent Akt-1 activation sequence resulting in T308 and S473 phosphorylations of the latter, respectively [16,17].